Pathophysiology of Clopidogrel in Ischemic Stroke, Role of Platelet microRNAs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F25%3A10503534" target="_blank" >RIV/00064165:_____/25:10503534 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/25:00142673 RIV/61988987:17110/25:A2603DN8 RIV/00216208:11110/25:10503534

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SQskMgDSf6" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SQskMgDSf6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33549/physiolres.935617" target="_blank" >10.33549/physiolres.935617</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pathophysiology of Clopidogrel in Ischemic Stroke, Role of Platelet microRNAs

Popis výsledku v původním jazyce

Variation in response to clopidogrel represents a significant clinical challenge in patients with ischemic stroke. Genetic polymorphisms cytochrome P450 2C19 (CYP2C19) are a known cause of resistance to clopidogrel. Platelet microRNAs (miRNAs) can modulate the efficacy of antiplatelet therapy. This study focuses solely on clopidogrel because it is the most widely used alternative to aspirin in patients with aspirin intolerance or contraindications. Our aim was to investigate its pharmacogenomic and epigenetic modulation in a targeted and homogeneous cohort. CYP2C19 genotypes are commonly reported as *1/*1 (wild type), *1/*2 (intermediate metabolizer), *2/*2 (poor metabolizer) and *2/*3 (poor metabolizer). These denote the number and type of loss-of-function alleles that affect clopidogrel metabolism. Clopidogrel treatment is typically a component of broader secondary prevention strategies, including lifestyle modifications, statins, and control of blood pressure. Relevant bibliographic references have been added to support the background statements provided in the introduction and methodology. To evaluate the expression of selected platelet miRNAs (miR-126-3p, miR-19a-3p, miR-19b-3p, miR-22-3p, miR-185-5p) in patients with ischemic stroke in relation to the CYP2C19 genotype (*1/*1,*1/*2, *2/*2) during clopidogrel treatment. Seventy patients treated with clopidogrel (75 mg daily) were enrolled. Patients were genotyped for the CYP2C19 *2 and *3 alleles by real-time polymerase chain reaction (polymerase chain reaction (PCR)) and miRNA expression was measured in plasma. All abbreviations used throughout the manuscript have been defined at their first appearance for the sake of clarity. No significant differences in miRNA expression were found between the genotypic groups (p &gt; 0.05). Patients with genotype *2/*2 (poor metabolizer) showed a trend towards higher levels of miR-126-3p and miR-185-5p (approximately 1.5 to 1.7 times) compared to *1/*1 (wild type). The clinical parameters did not differ significantly between the groups. Poor clopidogrel metabolizers can exhibit upregulation of some platelet miRNAs as a potential compensatory mechanism. This pilot study suggests a possible epigenetic modulation of the response to antiplatelet therapy through platelet miRNAs.

Název v anglickém jazyce

Pathophysiology of Clopidogrel in Ischemic Stroke, Role of Platelet microRNAs

Popis výsledku anglicky

Variation in response to clopidogrel represents a significant clinical challenge in patients with ischemic stroke. Genetic polymorphisms cytochrome P450 2C19 (CYP2C19) are a known cause of resistance to clopidogrel. Platelet microRNAs (miRNAs) can modulate the efficacy of antiplatelet therapy. This study focuses solely on clopidogrel because it is the most widely used alternative to aspirin in patients with aspirin intolerance or contraindications. Our aim was to investigate its pharmacogenomic and epigenetic modulation in a targeted and homogeneous cohort. CYP2C19 genotypes are commonly reported as *1/*1 (wild type), *1/*2 (intermediate metabolizer), *2/*2 (poor metabolizer) and *2/*3 (poor metabolizer). These denote the number and type of loss-of-function alleles that affect clopidogrel metabolism. Clopidogrel treatment is typically a component of broader secondary prevention strategies, including lifestyle modifications, statins, and control of blood pressure. Relevant bibliographic references have been added to support the background statements provided in the introduction and methodology. To evaluate the expression of selected platelet miRNAs (miR-126-3p, miR-19a-3p, miR-19b-3p, miR-22-3p, miR-185-5p) in patients with ischemic stroke in relation to the CYP2C19 genotype (*1/*1,*1/*2, *2/*2) during clopidogrel treatment. Seventy patients treated with clopidogrel (75 mg daily) were enrolled. Patients were genotyped for the CYP2C19 *2 and *3 alleles by real-time polymerase chain reaction (polymerase chain reaction (PCR)) and miRNA expression was measured in plasma. All abbreviations used throughout the manuscript have been defined at their first appearance for the sake of clarity. No significant differences in miRNA expression were found between the genotypic groups (p &gt; 0.05). Patients with genotype *2/*2 (poor metabolizer) showed a trend towards higher levels of miR-126-3p and miR-185-5p (approximately 1.5 to 1.7 times) compared to *1/*1 (wild type). The clinical parameters did not differ significantly between the groups. Poor clopidogrel metabolizers can exhibit upregulation of some platelet miRNAs as a potential compensatory mechanism. This pilot study suggests a possible epigenetic modulation of the response to antiplatelet therapy through platelet miRNAs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological Research

ISSN

0862-8408

e-ISSN

1802-9973

Svazek periodika

74

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

7

Strana od-do

669-675

Kód UT WoS článku

001568778000013

EID výsledku v databázi Scopus

2-s2.0-105015030552